A Phase II Trial With Safety Run-in of Neoadjuvant Therapy With an Aromatase Inhibitor in Combination With Durvalumab (MEDI4736) in Postmenopausal Patients With Hormone-Receptor-Positive Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Breast Cancer
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- Rate of Modified Preoperative Endocrine Prognostic Index (mPEPI) Score of 0
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
This study is to find out if an investigational drug called Durvalumab (MEDI4736) given together with a standard of care aromatase inhibitor drug can help people with breast cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Postmenopausal, defined as meeting criteria per protocol.
- •Clinical T2-T4c, any N, MO by American Joint Committee on Cancer staging, 8th edition, with the goal being definitive surgery after completion of neoadjuvant therapy. Tumor is palpable and its size can be measured bidimensionally by tape, ruler or caliper technique. Largest tumor diameter over 2.0 cm.
- •Pathologic confirmation of invasive breast cancer that is estrogen receptor (ER) positive as defined in the protocol.
- •Invasive breast cancer is Human Epidermal Growth Factor Receptor 2 (HER2) negative as defined in the protocol protocol.
- •Documentation of mammogram and ultrasound \[including ductal carcinoma in situ (DCIS) and invasive cancer\] of the diseased breast performed within 60 days prior to enrollment. Mammograms for the unaffected contralateral breast is required within 12 months prior to enrollment.
- •Adequate organ and marrow function, as defined in the protocol.
- •Participants must be willing to undergo a research biopsy at baseline and after one cycle of treatment and to provide tissue obtained at surgery for biomarker and correlative studies.
- •Participants must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- •If taking herbal or natural remedies that may have immune modulatory effects, participants must be willing to discontinue use prior to first dose of durvalumab.
Exclusion Criteria
- •Participation in another clinical study with an investigational product during the last 4 weeks.
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow up period of an interventional study.
- •Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema).
- •An excisional biopsy of this breast cancer. Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration.
- •Surgical axillary staging procedure prior to study entry. Note: Fine needle aspiration (FNA) or core needle biopsy of axillary node is permitted.
- •Treatment for this cancer including surgery, radiation therapy, chemotherapy, biotherapy, hormonal therapy or investigational agent prior to study entry.
- •Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
- •History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥ 5 years or adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease or adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ.
- •History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral ductal carcinoma in situ (DCIS) treated with radiotherapy or endocrine therapy or contralateral invasive breast cancer at any time.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection); systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid; or steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
Arms & Interventions
Safety Run In: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited. Six participants will be enrolled in the safety run in stage. If 1 or fewer of six participants have a DLT, expansion stage will open to enrollment.
Intervention: Durvalumab
Safety Run In: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited. Six participants will be enrolled in the safety run in stage. If 1 or fewer of six participants have a DLT, expansion stage will open to enrollment.
Intervention: Anastrozole 1mg
Safety Run In: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited. Six participants will be enrolled in the safety run in stage. If 1 or fewer of six participants have a DLT, expansion stage will open to enrollment.
Intervention: Letrozole 2.5mg
Safety Run In: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited. Six participants will be enrolled in the safety run in stage. If 1 or fewer of six participants have a DLT, expansion stage will open to enrollment.
Intervention: Exemestane 25 MG
Expansion: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited.
Intervention: Durvalumab
Expansion: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited.
Intervention: Anastrozole 1mg
Expansion: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited.
Intervention: Letrozole 2.5mg
Expansion: Durvalumab + Aromatase Inhibitor
Participants will be administered 1500 mg Durvalumab intravenously every 4 weeks for 6 cycles. Participants will also take standard of care 1 mg anastrozole daily by mouth for 6 months. Letrozole 2.5 mg or exemastane 25 mg may be substituted for anastrozole if an intolerance to anastrozole is exhibited.
Intervention: Exemestane 25 MG
Outcomes
Primary Outcomes
Rate of Modified Preoperative Endocrine Prognostic Index (mPEPI) Score of 0
Time Frame: 6 months
Modified preoperative endocrine prognostic index (mPEPI) of 0. Total PEPI score assigned to each patient is the sum of the risk points derived from the pathological (pT) stage, lymph node (pN) stage, Ki67 level, and estrogen receptor (ER) status of the surgical specimen. A hazard ratio (HR) in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. mPEPI score of 0 indicates a tumor size of 5 cm or less, negative lymph nodes, and Ki67 (proliferation index) of less than or equal to 2.7%. Drug combination will be determined to be efficacious if 7 or more participants achieve an mPEPI of 0.
Secondary Outcomes
- Clinical Complete Response (CR)(6 months)
- Clinical Partial Response (PR)(6 months)